Objective: Danshensu, a phenylpropanoid compound, is derived from the dry root and rhizome of Danshen (Salvia miltiorrhiza), a traditional Chinese medicinal herb. Evidence suggests that danshensu protects isolated rat hearts against ischemia/reperfusion injury by activating the protein kinase B (Akt)/extracellular signal-regulated kinase (ERK) pathway or by inhibiting autophagy and apoptosis through the activation of mammalian target of rapamycin (mTOR) signaling. Furthermore, danshensu promotes the postischemic regeneration of brain cells by upregulating the expression of brain-derived neurotrophic factor (BDNF) in the peri-infarct region. However, basic and clinical studies are needed to investigate the antidepressant effects danshensu and determine whether brain mTOR signaling and BDNF activation mediate these effects. The aforementioned need prompted us to conduct the present study. Methods: Using a C57BL/6 mouse model, we investigated the antidepressant-like effects of danshensu and the mechanisms that mediate these effects. To elucidate the mechanisms, we analyzed the roles of Akt/ERK–mTOR signaling and BDNF activation in mediating the antidepressant-like effects of danshensu. Results: Danshensu exerted its antidepressant-like effects by activating the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) of Akt/ERK–mTOR signaling and promoting BDNF release. Treatment with danshensu increased the level of glutamate receptor 1 phosphorylation at the protein kinase A site. Conclusion Our study may be the first to demonstrate that the antidepressant effects of danshensu are dependent on the activation of the AMPAR–mTOR signaling pathway, are correlated with the elevation of BDNF level, and facilitate the insertion of AMPAR into the postsynaptic membrane. This study also pioneers in unveiling the potential of danshensu against depressive disorders.

Objective: Danshensu, a phenylpropanoid compound, is derived from the dry root and rhizome of Danshen (Salvia miltiorrhiza), a traditional Chinese medicinal herb. Evidence suggests that danshensu protects isolated rat hearts against ischemia/reperfusion injury by activating the protein kinase B (Akt)/extracellular signal-regulated kinase (ERK) pathway or by inhibiting autophagy and apoptosis through the activation of mammalian target of rapamycin (mTOR) signaling. Furthermore, danshensu promotes the postischemic regeneration of brain cells by upregulating the expression of brain-derived neurotrophic factor (BDNF) in the peri-infarct region. However, basic and clinical studies are needed to investigate the antidepressant effects danshensu and determine whether brain mTOR signaling and BDNF activation mediate these effects. The aforementioned need prompted us to conduct the present study. Methods: Using a C57BL/6 mouse model, we investigated the antidepressant-like effects of danshensu and the mechanisms that mediate these effects. To elucidate the mechanisms, we analyzed the roles of Akt/ERK–mTOR signaling and BDNF activation in mediating the antidepressant-like effects of danshensu. Results: Danshensu exerted its antidepressant-like effects by activating the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) of Akt/ERK–mTOR signaling and promoting BDNF release. Treatment with danshensu increased the level of glutamate receptor 1 phosphorylation at the protein kinase A site. Conclusion Our study may be the first to demonstrate that the antidepressant effects of danshensu are dependent on the activation of the AMPAR–mTOR signaling pathway, are correlated with the elevation of BDNF level, and facilitate the insertion of AMPAR into the postsynaptic membrane. This study also pioneers in unveiling the potential of danshensu against depressive disorders.

Objective: Danshensu, a phenylpropanoid compound, is derived from the dry root and rhizome of Danshen (Salvia miltiorrhiza), a traditional Chinese medicinal herb. Evidence suggests that danshensu protects isolated rat hearts against ischemia/reperfusion injury by activating the protein kinase B (Akt)/extracellular signal-regulated kinase (ERK) pathway or by inhibiting autophagy and apoptosis through the activation of mammalian target of rapamycin (mTOR) signaling. Furthermore, danshensu promotes the postischemic regeneration of brain cells by upregulating the expression of brain-derived neurotrophic factor (BDNF) in the peri-infarct region. However, basic and clinical studies are needed to investigate the antidepressant effects danshensu and determine whether brain mTOR signaling and BDNF activation mediate these effects. The aforementioned need prompted us to conduct the present study. Methods: Using a C57BL/6 mouse model, we investigated the antidepressant-like effects of danshensu and the mechanisms that mediate these effects. To elucidate the mechanisms, we analyzed the roles of Akt/ERK–mTOR signaling and BDNF activation in mediating the antidepressant-like effects of danshensu. Results: Danshensu exerted its antidepressant-like effects by activating the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) of Akt/ERK–mTOR signaling and promoting BDNF release. Treatment with danshensu increased the level of glutamate receptor 1 phosphorylation at the protein kinase A site. Conclusion Our study may be the first to demonstrate that the antidepressant effects of danshensu are dependent on the activation of the AMPAR–mTOR signaling pathway, are correlated with the elevation of BDNF level, and facilitate the insertion of AMPAR into the postsynaptic membrane. This study also pioneers in unveiling the potential of danshensu against depressive disorders.

Objective: Danshensu, a phenylpropanoid compound, is derived from the dry root and rhizome of Danshen (Salvia miltiorrhiza), a traditional Chinese medicinal herb. Evidence suggests that danshensu protects isolated rat hearts against ischemia/reperfusion injury by activating the protein kinase B (Akt)/extracellular signal-regulated kinase (ERK) pathway or by inhibiting autophagy and apoptosis through the activation of mammalian target of rapamycin (mTOR) signaling. Furthermore, danshensu promotes the postischemic regeneration of brain cells by upregulating the expression of brain-derived neurotrophic factor (BDNF) in the peri-infarct region. However, basic and clinical studies are needed to investigate the antidepressant effects danshensu and determine whether brain mTOR signaling and BDNF activation mediate these effects. The aforementioned need prompted us to conduct the present study. Methods: Using a C57BL/6 mouse model, we investigated the antidepressant-like effects of danshensu and the mechanisms that mediate these effects. To elucidate the mechanisms, we analyzed the roles of Akt/ERK–mTOR signaling and BDNF activation in mediating the antidepressant-like effects of danshensu. Results: Danshensu exerted its antidepressant-like effects by activating the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) of Akt/ERK–mTOR signaling and promoting BDNF release. Treatment with danshensu increased the level of glutamate receptor 1 phosphorylation at the protein kinase A site. Conclusion Our study may be the first to demonstrate that the antidepressant effects of danshensu are dependent on the activation of the AMPAR–mTOR signaling pathway, are correlated with the elevation of BDNF level, and facilitate the insertion of AMPAR into the postsynaptic membrane. This study also pioneers in unveiling the potential of danshensu against depressive disorders.

Objective: Danshensu, a phenylpropanoid compound, is derived from the dry root and rhizome of Danshen (Salvia miltiorrhiza), a traditional Chinese medicinal herb. Evidence suggests that danshensu protects isolated rat hearts against ischemia/reperfusion injury by activating the protein kinase B (Akt)/extracellular signal-regulated kinase (ERK) pathway or by inhibiting autophagy and apoptosis through the activation of mammalian target of rapamycin (mTOR) signaling. Furthermore, danshensu promotes the postischemic regeneration of brain cells by upregulating the expression of brain-derived neurotrophic factor (BDNF) in the peri-infarct region. However, basic and clinical studies are needed to investigate the antidepressant effects danshensu and determine whether brain mTOR signaling and BDNF activation mediate these effects. The aforementioned need prompted us to conduct the present study. Methods: Using a C57BL/6 mouse model, we investigated the antidepressant-like effects of danshensu and the mechanisms that mediate these effects. To elucidate the mechanisms, we analyzed the roles of Akt/ERK–mTOR signaling and BDNF activation in mediating the antidepressant-like effects of danshensu. Results: Danshensu exerted its antidepressant-like effects by activating the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) of Akt/ERK–mTOR signaling and promoting BDNF release. Treatment with danshensu increased the level of glutamate receptor 1 phosphorylation at the protein kinase A site. Conclusion Our study may be the first to demonstrate that the antidepressant effects of danshensu are dependent on the activation of the AMPAR–mTOR signaling pathway, are correlated with the elevation of BDNF level, and facilitate the insertion of AMPAR into the postsynaptic membrane. This study also pioneers in unveiling the potential of danshensu against depressive disorders.

Background/Aims: Finite nucleos(t)ide analog (NA) therapy has been proposed as an alternative treatment strategy for chronic hepatitis B (CHB), but biomarkers for post-treatment monitoring are limited. We investigated whether measuring hepatitis B core-related antigen (HBcrAg) after NA cessation may stratify the risk of subsequent clinical relapse (CR). Methods: This retrospective multicenter analysis enrolled adults with CHB who were prospectively monitored after discontinuing entecavir or tenofovir with negative HBeAg and undetectable HBV DNA at the end of treatment (EOT). Patients with cirrhosis or malignancy were excluded. CR was defined as serum alanine aminotransferase > two times the upper limit of normal with recurrent viremia. We applied time-dependent Cox proportional hazard models to clarify the association between HBcrAg levels and subsequent CR. Results: The cohort included 203 patients (median age, 49.8 years; 76.8% male; 60.6% entecavir) who had been treated for a median of 36.9 months (interquartile range [IQR], 36.5–40.1). During a median post-treatment follow-up of 31.7 months (IQR, 16.7–67.1), CR occurred in 104 patients with a 5-year cumulative incidence of 54.8% (95% confidence interval [CI], 47.1–62.4%). Time-varying HBcrAg level was a significant risk factor for subsequent CR (adjusted hazard ratio [aHR], 1.53 per log U/mL; 95% CI, 1.12–2.08) with adjustment for EOT HBsAg, EOT anti-HBe, EOT HBcrAg and time-varying HBsAg. During follow-up, HBcrAg <1,000 U/mL predicted a lower risk of CR (aHR, 0.41; 95% CI, 0.21–0.81). Conclusions Dynamic measurement of HBcrAg after NA cessation is predictive of subsequent CR and may be useful to guide post-treatment monitoring.

Ulcerative colitis (UC) is a chronic inflammation of the gastrointestinal tract and is characterized by alternating periods of inflammation and remission. Although UC incidence is lower in Taiwan than in Western countries, its impact remains considerable, demanding updated guidelines for addressing local healthcare challenges and patient needs. The revised guidelines employ international standards and recent research, emphasizing practical implementation within the Taiwanese healthcare system. Since the inception of the guidelines in 2017, the Taiwan Society of Inflammatory Bowel Disease has acknowledged the need for ongoing revisions to incorporate emerging therapeutic options and evolving disease management practices. This updated guideline aims to align UC management with local contexts, ensuring comprehensive and context-specific recommendations, thereby raising the standard of care for UC patients in Taiwan. By adapting and optimizing international protocols for local relevance, these efforts seek to enhance health outcomes for patients with UC.

Crohn’s disease (CD) is a chronic, fluctuating inflammatory condition that primarily affects the gastrointestinal tract. Although the incidence of CD in Taiwan is lower than that in Western countries, the severity of CD presentation appears to be similar between Asia and the West. This observation indicates the urgency for devising revised guidelines tailored to the unique reimbursement system, and patient requirements in Taiwan. The core objectives of these updated guidelines include the updated treatment choices and the integration of the treat-to-target strategy into CD management, promoting the achievement of deep remission to mitigate complications and enhance the overall quality of life. Given the diversity in disease prevalence, severity, insurance policies, and access to medical treatments in Taiwan, a customized approach is imperative for formulating these guidelines. Such tailored strategies ensure that international standards are not only adapted but also optimized to local contexts. Since the inception of its initial guidelines in 2017, the Taiwan Society of Inflammatory Bowel Disease (TSIBD) has acknowledged the importance of continuous revisions for incorporating new therapeutic options and evolving disease management practices. The latest update leverages international standards and recent research findings focused on practical implementation within the Taiwanese healthcare system.

Objective: Emerging evidence suggests that air pollution exposure may increase the risk of Parkinson’s disease (PD). We aimed to investigate the association between exposure to fine particulate matter (PM2.5) and the risk of incident PD nationwide. Methods: We utilized data from the Taiwan National Health Insurance Research Database, which is spatiotemporally linked with air quality data from the Taiwan Environmental Protection Administration website. The study population consisted of participants who were followed from the index date (January 1, 2005) until the occurrence of PD or the end of the study period (December 31, 2017). Participants who were diagnosed with PD before the index date were excluded. To evaluate the association between exposure to PM2.5 and incident PD risk, we employed Cox regression to estimate the hazard ratio and 95% confidence interval (CI). Results: A total of 454,583 participants were included, with a mean (standard deviation) age of 63.1 (9.9) years and a male proportion of 50%. Over a mean follow-up period of 11.1 (3.6) years, 4% of the participants (n = 18,862) developed PD. We observed a significant positive association between PM2.5 exposure and the risk of PD, with a hazard ratio of 1.22 (95% CI, 1.20–1.23) per interquartile range increase in exposure (10.17 μg/m3) when adjusting for both SO2 and NO2. Conclusion We provide further evidence of an association between PM2.5 exposure and the risk of PD. These findings underscore the urgent need for public health policies aimed at reducing ambient air pollution and its potential impact on PD.

Background/Aims: Ineffective esophageal motility (IEM) is common in patients with gastroesophageal reflux disease (GERD) and can be associated with poor esophageal contraction reserve on multiple rapid swallows. Alterations in the esophageal microbiome have been reported in GERD, but the relationship to presence or absence of contraction reserve in IEM patients has not been evaluated. We aim to investigate whether contraction reserve influences esophageal microbiome alterations in patients with GERD and IEM. Methods: We prospectively enrolled GERD patients with normal endoscopy and evaluated esophageal motility and contraction reserve with multiple rapid swallows during high-resolution manometry. The esophageal mucosa was biopsied for DNA extraction and 16S ribosomal RNA gene V3-V4 (Illumina)/full-length (Pacbio) amplicon sequencing analysis. Results: Among the 56 recruited patients, 20 had normal motility (NM), 19 had IEM with contraction reserve (IEM-R), and 17 had IEM without contraction reserve (IEM-NR). Esophageal microbiome analysis showed a significant decrease in microbial richness in patients with IEM-NR when compared to NM. The beta diversity revealed different microbiome profiles between patients with NM or IEM-R and IEM-NR (P = 0.037). Several esophageal bacterial taxa were characteristic in patients with IEM-NR, including reduced Prevotella spp.and Veillonella dispar, and enriched Fusobacterium nucleatum. In a microbiome-based random forest model for predicting IEM-NR, an area under the receiver operating characteristic curve of 0.81 was yielded. Conclusions In symptomatic GERD patients with normal endoscopic findings, the esophageal microbiome differs based on contraction reserve among IEM. Absent contraction reserve appears to alter the physiology and microbiota of the esophagus.